Multi-ancestry investigation of the genomics of erectile dysfunction.

Erectile dysfunction is attributable to numerous biological and psychological issues, and its prevalence increases with age. We conducted genome-wide association studies of erectile dysfunction in AllofUs subjects of European and African ancestry, then meta-analyzed our findings with published datasets [NEuropean = 913,194 (136,867 cases); NAfrican = 125,315 (51,599 cases)]. We identified 40 independent variants in Europeans, two in Africans, and 51 cross-ancestry. In all analyses, the strongest effect variants mapped to a non-coding region known to regulate SIM1, previously associated with erectile dysfunction: rs78677597 (Europeans) (p = 5.32 × 10-139), and rs17185536 (Africans (p = 1.17 × 10-9) and cross-ancestry (p = 5.3 × 10-138)). Genetic correlations with psychiatric and health traits were moderate. Positive associations with phenotypes related to sexual drive may reflect ascertainment bias. This study is consistent with indications that erectile dysfunction is a complex trait influenced by multiple factors. Our findings emphasize the need to investigate genetic risk - SIM1 in particular further - to understand the mechanism through which they affect erectile function.